Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is one of the most common infectious diseases in women. The morbidity and economic impact are enormous, with over $2.5 billion spent annually on treatment. Further, recurrent infections are a significant problem despite appropriate antibiotic therapy of the index case. The high rates of recurrence, and the large numbers of women that end up in urology clinics due to their chronic recurrent UTIs highlights the need for a better understanding of the pathogenic mechanisms involved in this disease and the development of new and better therapies. The high frequency of same-strain recurrences supports the notion that a UPEC quiescent intracellular reservoir (QIR) can exist in the affected individual, and persist even after antibiotic therapy and urine cultures become sterile. Current diagnostic schemes for these bacteria are based on culture and do not distinguish between strains with high or low virulence potential.
Therefore, there is a need for an effective biomarker for urinary tract infections that avoids false negative results that occur when culture-based methods are applied during antibiotic therapy or when culture or nucleic acid-based methods are applied to patients in which bacteria are not actively shed into sampled fluids. In addition, there is a need for effective treatments that can cure urinary tract infections and prevent infection by quiescent intracellular reservoirs of pathogenic bacteria that are the source of so many recurrent urinary tract infections.
Further, due to the high incidence of UTI, antibiotic resistance is common. As clinicians struggle with the paucity of mechanistically new antibiotics targeting Gram-negative pathogens and dramatic increases in antibiotic resistance, UTIs are increasingly difficult to manage. As a result, UTIs present a high economic burden marked by increasing healthcare costs. The potential for Gram-negative UTIs to progress to systemic infections motivates aggressive antibiotic use, which drives the selective evolution of antibiotic resistant strains among gut microbiota. Along with concerns of treatment-resistant infections, there is a growing appreciation that current broad-spectrum antibiotic strategies cause detrimental changes to the human microbiome. Thus, there is a need to strategically treat UTI such that if the causative strain is susceptible to a narrower spectrum antibiotic, then that antibiotic is used thereby saving use of broad spectrum antibiotics to only when necessary. Further, strategic treatment of UTI by treating with an antibiotic in which the causative strain is susceptible reduces the likelihood of treatment failures thereby reducing the incidence of developing a systemic infection due to spread of the resistant organism.